title: Cold exposure promotes atherosclerotic plaque growth and instability via UCP1-dependent lipolysis.
abstract: Molecular mechanisms underlying the cold-associated high cardiovascular risk remain unknown. Here, we show that the cold-triggered food-intake-independent lipolysis significantly increased plasma levels of small low-density lipoprotein (LDL) remnants, leading to accelerated development of atherosclerotic lesions in mice. In two genetic mouse knockout models (apolipoprotein E(-/-) [ApoE(-/-)] and LDL receptor(-/-) [Ldlr(-/-)] mice), persistent cold exposure stimulated atherosclerotic plaque growth by increasing lipid deposition. Furthermore, marked increase of inflammatory cells and plaque-associated microvessels were detected in the cold-acclimated ApoE(-/-) and Ldlr(-/-) mice, leading to plaque instability. Deletion of uncoupling protein 1 (UCP1), a key mitochondrial protein involved in thermogenesis in brown adipose tissue (BAT), in the ApoE(-/-) strain completely protected mice from the cold-induced atherosclerotic lesions. Cold acclimation markedly reduced plasma levels of adiponectin, and systemic delivery of adiponectin protected ApoE(-/-) mice from plaque development. These findings provide mechanistic insights on low-temperature-associated cardiovascular risks.
authors.affiliation: The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University Qilu Hospital, Jinan, Shandong 250012, People's Republic of China.
authors.forename: Mei
authors.initials: M
authors.lastname: Dong
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
authors.forename: Sharon
authors.initials: S
authors.lastname: Lim
authors.forename: Ziquan
authors.initials: Z
authors.lastname: Cao
authors.forename: Jennifer
authors.initials: J
authors.lastname: Honek
authors.forename: Huixia
authors.initials: H
authors.lastname: Lu
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Takahiro
authors.initials: T
authors.lastname: Seki
authors.forename: Kayoko
authors.initials: K
authors.lastname: Hosaka
authors.forename: Eric
authors.initials: E
authors.lastname: Wahlberg
authors.forename: Jianmin
authors.initials: J
authors.lastname: Yang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Toste
authors.initials: T
authors.lastname: Länne
authors.forename: Baocun
authors.initials: B
authors.lastname: Sun
authors.forename: Xuri
authors.initials: X
authors.lastname: Li
authors.forename: Yizhi
authors.initials: Y
authors.lastname: Liu
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yihai
authors.initials: Y
authors.lastname: Cao
mesh_terms: D000064:Acclimatization / Q000502:physiology; D052242:Adiponectin / Q000097:blood; D002001:Adipose Tissue, Brown / Q000502:physiology; D000328:Adult; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D050197:Atherosclerosis / Q000209:etiology* / Q000503:physiopathology*; D008078:Cholesterol, LDL / Q000097:blood; D003080:Cold Temperature / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D050356:Lipid Metabolism / Q000502:physiology; D008066:Lipolysis / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D010865:Pilot Projects; D058226:Plaque, Atherosclerotic / Q000209:etiology* / Q000503:physiopathology*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D022722:Thermogenesis / Q000502:physiology; D000071256:Uncoupling Protein 1
chemical_list: D052242:Adiponectin; D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D007473:Ion Channels; D024101:Mitochondrial Proteins; D011973:Receptors, LDL; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1